Effects of acute and chronic strength training on skeletal muscle autophagy in frail elderly men and women.

Aging is associated with alterations in skeletal muscle autophagy, potentially affecting both muscle mass and quality in a negative manner. Strength training with protein supplementation has been reported to improve both muscle mass and quality in frail elderly individuals, but whether improvements are accompanied by alterations in protein quality control is not known. To address this issue, we investigated protein degradation markers in skeletal muscle biopsies (m. vastus lateralis) from twenty-four frail elderly men and women (86 ± 7 yr) after acute and chronic (10 weeks) strength training with protein supplementation (ST + PRO) or protein supplementation alone (PRO). Acute increases in mRNA expression of genes related to the ubiquitin proteasome system (MuRF-1, MUSA1), autophagy (ATG7, LC3, p62), and mitochondrial fission (DRP1) were observed after the first, but not after the last training session in ST + PRO. Acute changes in gene expression were accompanied by changes in protein levels of both LC3-I and LC3-II. Hence, the acute training-induced activation of proteasomal degradation and autophagy seems to depend on training status, with activation in the untrained, but not trained state. The ten-week training intervention did not affect basal levels of autophagy mRNAs and proteins, and neither markers of the ubiquitin-proteasome system. This suggests that a relatively short period of strength training may not be sufficient to increase the basal rate of protein degradation in frail elderly.

Strength training and protein supplementation improve muscle mass, strength, and function in mobility-limited older adults: a randomized controlled trial.

BACKGROUND: Adaptation to strength training in very old mobility-limited individuals is not fully characterized. Therefore, the aim of this study was to perform a thorough investigation of the adaptation to a lower body strength training regime in this population, with particular emphasis on the relationship between changes in selected variables. METHODS: Twenty-two mobility-limited older men and women (85 ± 6 years) were randomized to either a group performing 30 min of heavy-load strength training three times a week, with daily protein supplementation, for 10 weeks (ST), or a control group. End points were leg lean mass assessed by DXA, muscle thickness assessed by ultrasound, isometric and dynamic strength, rate of torque development, and functional capacity. RESULTS: Leg lean mass increased from baseline in ST (0.7 ± 0.3 kg), along with increased thickness of vastus lateralis (4.4 ± 3.2%), rectus femoris (6.7 ± 5.1%), and vastus intermedius (5.8 ± 5.9%). The hypertrophy was accompanied by improved knee extensor strength (20-23%) and functional performance (7-11%). In ST, neither the change in leg lean mass nor muscle thickness correlated with changes in muscle strength. However, a strong correlation was observed between the change in isometric strength and gait velocity (r = 0.70). CONCLUSIONS: The mismatch between gains in muscle size and strength suggests that muscle quality-related adaptations contributed to the increases in strength. The correlations observed between improvements in strength and function suggests that interventions eliciting large improvements in strength may also be superior in terms of functional gains in this population.

Native Whey Induces Similar Adaptation to Strength Training as Milk, despite Higher Levels of Leucine, in Elderly Individuals.

BACKGROUND: Large amounts of protein (40 g) or supplementing suboptimal servings of protein with leucine are able to overcome the anabolic resistance in elderly muscle. Our aim was to compare the effects of supplementation of native whey, high in leucine, with milk on gains in muscle mass and strength during a period of strength training, in elderly individuals. METHODS: In this double-blinded, randomized, controlled study, a total of 30 healthy men and women received two daily servings of 20 g of either milk protein or native whey, during an 11-week strength training intervention. Muscle strength, lean mass, m. vastus lateralis thickness, muscle fiber area, and resting and post-exercise phosphorylation of p70S6K, 4E-BP1, and eEF-2 were assessed prior to and after the intervention period. RESULTS: Muscle mass and strength increased, by all measures applied in both groups (p < 0.001), with no differences between groups (p > 0.25). p70S6K phosphorylation increased (~1000%, p < 0.045) 2 h after exercise in the untrained and trained state, with no differences between supplements. Total and phosphorylated mTORC-1 decreased after training. CONCLUSION: Supplementation with milk or native whey during an 11-week strength training period increased muscle mass and strength similarly in healthy elderly individuals.

No Difference between Spray Dried Milk and Native Whey Supplementation with Strength Training.

BACKGROUND: A rapid digestibility and high leucine content are considered important for maximal stimulation of muscle protein synthesis. Consequently, with these properties, native whey may hold greater anabolic potential than milk, when supplemented in combination with strength training. Our aim was to compare the effects of supplementation with milk or native whey, during a 12-wk strength training period, on gains in muscle mass and strength in young adults. METHODS: In this double-blinded, randomized, controlled study a total of 40 untrained young men and women received two daily servings of either milk or native whey containing 20 g of protein, during a 12-wk strength training intervention. Muscle strength, lean mass, thigh muscle cross-sectional area, m. vastus lateralis thickness and muscle fiber cross-sectional area were assessed before and after the training period. In addition, the acute phosphorylation of the anabolic kinases p70S6K, 4E-BP1 and eEF-2 in response to a standardized workout and supplementation was investigated before and after the 12-wk training period. RESULTS: Muscle mass and strength increased, by all measures applied (5%-16%, P < 0.001), with no differences between groups (P > 0.25). p70S6K phosphorylation increased (~1000%, P < 0.02) 2 h after exercise in the untrained and trained state, but no differences in anabolic signaling were observed between supplements (P > 0.40). No correlation between these acute measures and changes in muscle mass or strength were observed. CONCLUSION: Supplementation with milk or native whey during a 12-wk strength training period did not differentially affect muscle mass and strength in young untrained individuals.

Native whey protein with high levels of leucine results in similar post-exercise muscular anabolic responses as regular whey protein: a randomized controlled trial.

BACKGROUND: Protein intake is essential to maximally stimulate muscle protein synthesis, and the amino acid leucine seems to possess a superior effect on muscle protein synthesis compared to other amino acids. Native whey has higher leucine content and thus a potentially greater anabolic effect on muscle than regular whey (WPC-80). This study compared the acute anabolic effects of ingesting 2 × 20 g of native whey protein, WPC-80 or milk protein after a resistance exercise session. METHODS: A total of 24 young resistance trained men and women took part in this double blind, randomized, partial crossover, controlled study. Participants received either WPC-80 and native whey (n = 10), in a crossover design, or milk (n = 12). Supplements were ingested immediately (20 g) and two hours after (20 g) a bout of heavy-load lower body resistance exercise. Blood samples and muscle biopsies were collected to measure plasma concentrations of amino acids by gas-chromatography mass spectrometry, muscle phosphorylation of p70S6K, 4E-BP1 and eEF-2 by immunoblotting, and mixed muscle protein synthesis by use of [2H5]phenylalanine-infusion, gas-chromatography mass spectrometry and isotope-ratio mass spectrometry. Being the main comparison, differences between native whey and WPC-80 were analysed by a one-way ANOVA and comparisons between the whey supplements and milk were analysed by a two-way ANOVA. RESULTS: Native whey increased blood leucine concentrations more than WPC-80 and milk (P < 0.05). Native whey ingestion induced a greater phosphorylation of p70S6K than milk 180 min after exercise (P = 0.03). Muscle protein synthesis rates increased 1-3 h hours after exercise with WPC-80 (0.119%), and 1-5 h after exercise with native whey (0.112%). Muscle protein synthesis rates were higher 1-5 h after exercise with native whey than with milk (0.112% vs. 0.064, P = 0.023). CONCLUSIONS: Despite higher-magnitude increases in blood leucine concentrations with native whey, it was not superior to WPC-80 concerning effect on muscle protein synthesis and phosphorylation of p70S6K during a 5-h post-exercise period. Native whey increased phosphorylation of p70S6K and muscle protein synthesis rates to a greater extent than milk during the 5-h post exercise period. TRIAL REGISTRATION: This study was retrospectively registered at clinicaltrials.gov as NCT02968888.

Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trial.

In this double-blind, randomised, controlled trial, we investigated the effects of vitamin C and E supplementation on endurance training adaptations in humans. Fifty-four young men and women were randomly allocated to receive either 1000 mg of vitamin C and 235 mg of vitamin E or a placebo daily for 11 weeks. During supplementation, the participants completed an endurance training programme consisting of three to four sessions per week (primarily of running), divided into high-intensity interval sessions [4-6 × 4-6 min; >90% of maximal heart rate (HRmax)] and steady state continuous sessions (30-60 min; 70-90% of HRmax). Maximal oxygen uptake (VO2 max ), submaximal running and a 20 m shuttle run test were assessed and blood samples and muscle biopsies were collected, before and after the intervention. Participants in the vitamin C and E group increased their VO2 max (mean ± s.d.: 8 ± 5%) and performance in the 20 m shuttle test (10 ± 11%) to the same degree as those in the placebo group (mean ± s.d.: 8 ± 5% and 14 ± 17%, respectively). However, the mitochondrial marker cytochrome c oxidase subunit IV (COX4) and cytosolic peroxisome proliferator-activated receptor-γ coactivator 1 α (PGC-1α) increased in the m. vastus lateralis in the placebo group by 59 ± 97% and 19 ± 51%, respectively, but not in the vitamin C and E group (COX4: -13 ± 54%; PGC-1α: -13 ± 29%; P ≤ 0.03, between groups). Furthermore, mRNA levels of CDC42 and mitogen-activated protein kinase 1 (MAPK1) in the trained muscle were lower in the vitamin C and E group than in the placebo group (P ≤ 0.05). Daily vitamin C and E supplementation attenuated increases in markers of mitochondrial biogenesis following endurance training. However, no clear interactions were detected for improvements in VO2 max and running performance. Consequently, vitamin C and E supplementation hampered cellular adaptations in the exercised muscles, and although this did not translate to the performance tests applied in this study, we advocate caution when considering antioxidant supplementation combined with endurance exercise.

G-CSF enhances the proliferation and mobilization, but not the maturation rate, of murine myeloid cells.

OBJECTIVES: Whether G-CSF enhances the maturation of neutrophilic granulocytes or just accelerates the mobilization of mature and maturing granulocytes from bone marrow to blood, or both, is not clear. Using an in vivo culture system where such mobilization cannot take place, we previously showed that G-CSF did not accelerate maturation. To further clarify the role of G-CSF, we now have examined its effect on murine granulopoiesis in situ. METHODS: Murine bone marrow precursors in S-phase were labeled with BrdU, and hematopoiesis stimulated by the long-acting G-CSF compound pegfilgrastim (peg-G-CSF). Performing flow cytometric analysis of incorporated BrdU and the granulocyte maturation antigen Gr1, we investigated the cell flux from the proliferative to the non-proliferative granulocyte compartments in bone marrow and further from bone marrow to blood. RESULTS: Peg-G-CSF mobilized neutrophils from bone marrow to blood and markedly increased their concentration in blood for several days. It also increased the proliferation of precursor cells. Newly produced, less mature granulocytes (Gr1(+) BrdU(+)) travelled faster to blood in treated mice than in controls. The flow cytometric and cell density analyses of the bone marrow cells showed that peg-G-CSF skewed the population toward less mature cells, mainly because of the mobilization of granulocytes to blood. CONCLUSIONS: Collectively, our data do not support the notion that G-CSF accelerates murine granulocyte maturation per se.